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1.
Circulation ; 142(12): 1176-1189, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32755393

RESUMO

BACKGROUND: Severe acute respiratory syndrome corona virus 2 infection causes severe pneumonia (coronavirus disease 2019 [COVID-19]), but the mechanisms of subsequent respiratory failure and complicating renal and myocardial involvement are poorly understood. In addition, a systemic prothrombotic phenotype has been reported in patients with COVID-19. METHODS: A total of 62 subjects were included in our study (n=38 patients with reverse transcriptase polymerase chain reaction-confirmed COVID-19 and n=24 non-COVID-19 controls). We performed histopathologic assessment of autopsy cases, surface marker-based phenotyping of neutrophils and platelets, and functional assays for platelet, neutrophil functions, and coagulation tests, as well. RESULTS: We provide evidence that organ involvement and prothrombotic features in COVID-19 are linked by immunothrombosis. We show that, in COVID-19, inflammatory microvascular thrombi are present in the lung, kidney, and heart, containing neutrophil extracellular traps associated with platelets and fibrin. Patients with COVID-19 also present with neutrophil-platelet aggregates and a distinct neutrophil and platelet activation pattern in blood, which changes with disease severity. Whereas cases of intermediate severity show an exhausted platelet and hyporeactive neutrophil phenotype, patients severely affected with COVID-19 are characterized by excessive platelet and neutrophil activation in comparison with healthy controls and non-COVID-19 pneumonia. Dysregulated immunothrombosis in severe acute respiratory syndrome corona virus 2 pneumonia is linked to both acute respiratory distress syndrome and systemic hypercoagulability. CONCLUSIONS: Taken together, our data point to immunothrombotic dysregulation as a key marker of disease severity in COVID-19. Further work is necessary to determine the role of immunothrombosis in COVID-19.


Assuntos
Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Insuficiência Respiratória/etiologia , Betacoronavirus/genética , Betacoronavirus/isolamento & purificação , Transtornos da Coagulação Sanguínea/diagnóstico , Transtornos da Coagulação Sanguínea/etiologia , Plaquetas/citologia , Plaquetas/metabolismo , Plaquetas/patologia , Estudos de Casos e Controles , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Armadilhas Extracelulares/metabolismo , Humanos , Rim/patologia , Pulmão/patologia , Neutrófilos/citologia , Neutrófilos/metabolismo , Neutrófilos/patologia , Pandemias , Fenótipo , Ativação Plaquetária , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Insuficiência Respiratória/diagnóstico , Índice de Gravidade de Doença , Trombose/complicações , Trombose/diagnóstico
2.
PLoS One ; 15(8): e0236946, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764790

RESUMO

Hemodialysis catheters are used to support blood filtration, yet there are multiple fundamentally different approaches to catheter tip design with no clear optimal solution. Side-holes have been shown to increase flow rates and decrease recirculation but have been associated with clotting/increased infection rates. This study investigates the impact of changing the shape, size and number of side-holes on a simple symmetric tip catheter by evaluating the velocity, shear stress and shear rate of inflowing blood. A platelet model is used to examine the residence time and shear history of inflowing platelets. The results show that side-holes improve the theoretical performance of the catheters, reducing the maximum velocity and shear stress occurring at the tip compared to non-side-hole catheters. Increasing the side-hole area improved performance up to a point, past which not all inflow through the hole was captured, and instead a small fraction slowly 'washed-out' through the remainder of the tip resulting in greater residence times and increasing the likelihood of platelet adhesion. An oval shaped hole presents a lower chance of external fibrin formation compared to a circular hole, although this would also be influenced by the catheter material surface topology which is dependent on the manufacturing process. Overall, whilst side-holes may be associated with increased clotting and infection, this can be reduced when side-hole geometry is correctly implemented though; a sufficient area for body diameter (minimising residence time) and utilising angle-cut, oval shaped holes (reducing shear stress and chances of fibrin formation partially occluding holes).


Assuntos
Cateteres , Diálise Renal/instrumentação , Velocidade do Fluxo Sanguíneo , Plaquetas/citologia , Cateteres/estatística & dados numéricos , Biologia Computacional , Simulação por Computador , Desenho de Equipamento , Hemodinâmica , Humanos , Hidrodinâmica , Modelos Cardiovasculares , Adesividade Plaquetária
3.
PLoS Negl Trop Dis ; 14(7): e0007656, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32687542

RESUMO

Platelets drive endothelial cell activation in many diseases. However, if this occurs in Plasmodium vivax malaria is unclear. As platelets have been reported to be activated and to play a role in inflammatory response during malaria, we hypothesized that this would correlate with endothelial alterations during acute illness. We performed platelet flow cytometry of PAC-1 and P-selectin. We measured platelet markers (CXCL4, CD40L, P-selectin, Thrombopoietin, IL-11) and endothelial activation markers (ICAM-1, von Willebrand Factor and E-selectin) in plasma with a multiplex-based assay. The values of each mediator were used to generate heatmaps, K-means clustering and Principal Component analysis. In addition, we determined pair-wise Pearson's correlation coefficients to generate correlation networks. Platelet counts were reduced, and mean platelet volume increased in malaria patients. The activation of circulating platelets in flow cytometry did not differ between patients and controls. CD40L levels (Median [IQ]: 517 [406-651] vs. 1029 [732-1267] pg/mL, P = 0.0001) were significantly higher in patients, while P-selectin and CXCL4 showed a nonsignificant trend towards higher levels in patients. The network correlation approach demonstrated the correlation between markers of platelet and endothelial activation, and the heatmaps revealed a distinct pattern of activation in two subsets of P. vivax patients when compared to controls. Although absolute platelet activation was not strong in uncomplicated vivax malaria, markers of platelet activity and production were correlated with higher endothelial cell activation, especially in a specific subset of patients.


Assuntos
Plaquetas/citologia , Malária Vivax/sangue , Adulto , Plaquetas/metabolismo , Ligante de CD40/genética , Ligante de CD40/metabolismo , Selectina E/genética , Selectina E/metabolismo , Células Endoteliais/metabolismo , Feminino , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-11/genética , Interleucina-11/metabolismo , Malária Vivax/genética , Malária Vivax/metabolismo , Masculino , Selectina-P/genética , Selectina-P/metabolismo , Ativação Plaquetária , Contagem de Plaquetas , Adulto Jovem
4.
Proc Natl Acad Sci U S A ; 117(32): 18969-18976, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32719144

RESUMO

Blood platelets are formed by fragmentation of long membrane extensions from bone marrow megakaryocytes in the blood flow. Using lattice-Boltzmann/immersed boundary simulations we propose a biological Rayleigh-Plateau instability as the biophysical mechanism behind this fragmentation process. This instability is akin to the surface tension-induced breakup of a liquid jet but is driven by active cortical processes including actomyosin contractility and microtubule sliding. Our fully three-dimensional simulations highlight the crucial role of actomyosin contractility, which is required to trigger the instability, and illustrate how the wavelength of the instability determines the size of the final platelets. The elasto-hydrodynamic origin of the fragmentation explains the strong acceleration of platelet biogenesis in the presence of an external flow, which we observe in agreement with experiments. Our simulations then allow us to disentangle the influence of specific flow conditions: While a homogeneous flow with uniform velocity leads to the strongest acceleration, a shear flow with a linear velocity gradient can cause fusion events of two developing platelet-sized swellings during fragmentation. A fusion event may lead to the release of larger structures which are observable as preplatelets in experiments. Together, our findings strongly indicate a mainly physical origin of fragmentation and regulation of platelet size in flow-accelerated platelet biogenesis.


Assuntos
Plaquetas/química , Actomiosina/química , Actomiosina/metabolismo , Animais , Biofísica , Velocidade do Fluxo Sanguíneo , Plaquetas/citologia , Hidrodinâmica , Camundongos
5.
Bratisl Lek Listy ; 121(4): 287-292, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32356444

RESUMO

OBJECTIVES: The aim of our study was to assess the diagnostic value of neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and red blood cell distribution width (RDW) in children with lymphadenopathy (LAP). METHODS: Between January, 2009 and December, 2018, 190 children who underwent excisional lymph node biopsy due to enlarged lymph nodes were included. The clinical and laboratory features of pediatric patients with lymph node enlargement, histopathological examination of the lymph node, and the role of complete blood count parameters in the differentiation of reactive and malignant LAP were analyzed retrospectively. RESULTS: In total, 139 (73.2 %) children had pathologically confirmed reactive LAP and 51 (26.8 %) were diagnosed with lymphoma. Compared with the reactive LAP group, median values for NLR, MLR, PLR, and RDW were significantly higher in children with lymphoma (p < 0.01). According to receiver operating characteristic curve analysis performed for distinguishing between reactive LAP and lymphomas, the area under curves of NLR, MLR, PLR, and RDW were 0.75, 0.76, 0.71, and 0.61, respectively. CONCLUSIONS: Children with histologically proven lymphoma have higher NLR, MLR, PLR, and RDW values than children with reactive LAP. NLR, MLR, PLR, and RDW tests, which can be performed even in primary health care centers, may be useful markers to determine which patients with LAP should be referred to the advanced center at an early stage for biopsy (Tab. 4, Fig. 2, Ref. 26).


Assuntos
Plaquetas/citologia , Índices de Eritrócitos , Linfadenopatia/diagnóstico , Linfócitos/citologia , Linfoma/diagnóstico , Monócitos/citologia , Neutrófilos/citologia , Criança , Humanos , Linfadenopatia/sangue , Linfoma/sangue , Prognóstico , Estudos Retrospectivos
6.
Rev Assoc Med Bras (1992) ; 66(2): 133-138, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32428146

RESUMO

OBJECTIVE: Periodontitis may stimulate infectious and immune response and cause the development of atherogenesis, coronary heart disease, and myocardial infarction. The aim of this study was to compare the plateletcrit (PCT) and mean platelet volume (MPV) levels derived from complete blood count (CBC) tests in patients suffering from stage 3 periodontitis with those of healthy individuals without periodontal disease. METHODS: The study included 57 patients (28 females and 29 males) with Stage 3 Periodontitis and 57 volunteering individuals (31 females and 26 males) who were periodontally healthy. The age of study participants ranged from 18 to 50 years. Their periodontal condition was investigated with probing depth (PD), clinical attachment level, bleeding on probing, and plaque index. Leukocyte (WBC) and erythrocyte count (RBC), hemoglobin (Hb) and hematocrit (HCT) levels, mean corpuscular volume (MCV) and red cell distribution width (RDW), thrombocyte count, mean platelet volume (MPV), plateletcrit (PCT ), and neutrophil and lymphocyte counts were evaluated based on the CBC test results of the study participants. RESULTS: PCT, WBC, Neutrophil, and MPV values were found to be significantly higher in the periodontitis group (p<0.05). There were no significant differences in RBC counts, Hb, HCT, MCV, RDW, and platelet and lymphocyte counts between the two study groups (p>0.05). CONCLUSIONS: PCT and MPV levels may be a more useful marker to determine an increased thrombotic state and inflammatory response in periodontal diseases.


Assuntos
Plaquetas/citologia , Volume Plaquetário Médio , Periodontite/sangue , Adolescente , Adulto , Contagem de Células Sanguíneas , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice Periodontal , Valores de Referência , Estatísticas não Paramétricas , Adulto Jovem
7.
Transfusion ; 60(5): 974-985, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32357261

RESUMO

BACKGROUND: The high incidence of septic transfusion reactions (STRs) led to testing being mandated by AABB from 2004. This was implemented by primary culture of single-donor apheresis platelets (APs) from 2004 and prestorage pooled platelets (PSPPs) from 2007. STUDY DESIGN/METHODS: Platelet (PLT) aliquots were cultured at issue and transfusion reactions evaluated at our hospital. Bacterial contamination and STR rates (shown as rates per million transfusions in Results) were evaluated before and after introduction of primary culture by blood centers that used a microbial detection system (BacT/ALERT, bioMerieux) or enhanced bacterial detection system (eBDS, Haemonetics). RESULTS: A total of 28,457 PLTs were cultured during pre-primary culture periods (44.7% APs; 55.3% at-issue pooled PLTs [AIPPs]) and 97,595 during post-primary culture periods (79.3% APs; 20.7% PSPPs). Forty-three contaminated units were identified in preculture and 34 in postculture periods (rates, 1511 vs. 348; p < 0.0001). Contamination rates of APs were significantly lower than AIPPs in the preculture (393 vs. 2415; p < 0.0001) but not postculture period compared to PSPPs (387 vs. 198; p = 0.9). STR rates (79 vs. 90; p = 0.98) were unchanged with APs but decreased considerably with pooled PLTs (826 vs. 50; p = 0.0006). Contamination (299 vs. 324; p = 0.84) and STR rates (25 vs. 116; p = 0.22) were similar for PLTs tested by BacT/ALERT and eBDS primary culture methods. A change in donor skin preparation method in 2012 was associated with decreased contamination and STR rates. CONCLUSION: Primary culture significantly reduced bacterial contamination and STR associated with pooled but not AP PLTs. Measures such as secondary testing near time of use or pathogen reduction are needed to further reduce STRs.


Assuntos
Infecções Bacterianas/epidemiologia , Contaminação de Medicamentos/estatística & dados numéricos , Transfusão de Plaquetas , Cultura Primária de Células , Sepse/epidemiologia , Reação Transfusional/epidemiologia , Centros Médicos Acadêmicos , Adulto , Infecções Bacterianas/sangue , Infecções Bacterianas/transmissão , Remoção de Componentes Sanguíneos/efeitos adversos , Remoção de Componentes Sanguíneos/história , Remoção de Componentes Sanguíneos/normas , Remoção de Componentes Sanguíneos/estatística & dados numéricos , Plaquetas/citologia , Plaquetas/microbiologia , Segurança do Sangue/efeitos adversos , Segurança do Sangue/história , Segurança do Sangue/estatística & dados numéricos , Transfusão de Sangue/história , Transfusão de Sangue/estatística & dados numéricos , Células Cultivadas , Criança , História do Século XX , História do Século XXI , Humanos , Incidência , Transfusão de Plaquetas/efeitos adversos , Transfusão de Plaquetas/história , Transfusão de Plaquetas/estatística & dados numéricos , Cultura Primária de Células/história , Cultura Primária de Células/normas , Cultura Primária de Células/estatística & dados numéricos , Estudos Retrospectivos , Sepse/sangue , Sepse/etiologia , Reação Transfusional/microbiologia , Estados Unidos/epidemiologia
8.
Transfusion ; 60(5): 922-931, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32358836

RESUMO

BACKGROUND: There have been no prior investigations of the cost effectiveness of transfusion strategies for trauma resuscitation. The Pragmatic, Randomized, Optimal Platelet and Plasma Ratios (PROPPR) study was a Phase III multisite, randomized trial in 680 subjects comparing the efficacy of 1:1:1 transfusion ratios of plasma and platelets to red blood cells with the 1:1:2 ratio. We hypothesized that 1:1:1 transfusion results in an acceptable incremental cost-effectiveness ratio, when estimated using patients' age-specific life expectancy and cost of care during the 30-day PROPPR trial period. STUDY DESIGN AND METHODS: International Classification of Diseases, Ninth Revision codes were prospectively collected, and subjects were matched 1:2 to subjects in the Healthcare Utilization Program State Inpatient Data to estimate cost weights. We used a decision tree analysis, combined with standard costs and estimated years of expected survival to determine the cost effectiveness of the two treatments. RESULTS: The 1:1:1 group had higher overall costs for the blood products but were more likely to achieve hemostasis and decreased hemorrhagic death by 24 hours (p = 0.006). For every 100 patients treated in the 1:1:1 group, eight more achieved hemostasis than in the 1:1:2 group. At 30 days, the total hospital cost per 100 patients was $5.6 million in the 1:1:1 group compared with $5.0 million in the 1:1:2 group. For each 100 patients, the 1:1:1 group had 218.5 more years of life expectancy. This was at a cost of $2994 per year gained. CONCLUSION: The 1:1:1 transfusion ratio in severely injured hemorrhaging trauma patients is a very cost-effective strategy for increasing hemostasis and decreasing trauma deaths.


Assuntos
Transfusão de Sangue/economia , Transfusão de Sangue/métodos , Adolescente , Adulto , Contagem de Células Sanguíneas/economia , Plaquetas/citologia , Transfusão de Sangue/mortalidade , Transfusão de Sangue/estatística & dados numéricos , Análise Custo-Benefício , Contagem de Eritrócitos , Transfusão de Eritrócitos/economia , Transfusão de Eritrócitos/métodos , Transfusão de Eritrócitos/mortalidade , Transfusão de Eritrócitos/estatística & dados numéricos , Eritrócitos/citologia , Feminino , Hemorragia/sangue , Hemorragia/mortalidade , Hemorragia/terapia , Mortalidade Hospitalar , Humanos , Tempo de Internação/economia , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Plasma/citologia , Transfusão de Plaquetas/economia , Transfusão de Plaquetas/métodos , Transfusão de Plaquetas/mortalidade , Transfusão de Plaquetas/estatística & dados numéricos , Ressuscitação/mortalidade , Ressuscitação/estatística & dados numéricos , Adulto Jovem
9.
PLoS One ; 15(4): e0230507, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32255777

RESUMO

The efficiency of in vitro platelet production is considerably low compared with physiological activity due to the lack of pivotal factors that are essential in vivo. We developed an ex vivo platelet production system, introducing human megakaryocytes into an isolated porcine thighbone and culturing in closed circuit. The efficiency of the ex vivo platelet production system was compared to those in vivo and in vitro. CD61+ platelet-like cells were counted by immunostaining and flow cytometry. Results showed that 4.41 ± 0.27 × 103 CD61+ platelet-like cells were produced by 1 × 103 megakaryocytes in the ex vivo system, while 3.80 ± 0.87 × 103 and 0.12 ± 0.02 × 103 were produced in the in vivo and in vitro systems, respectively. Notably, ex vivo and in vitro production systems generated cells that responded well to thrombin stimulation and expressed functional molecules, such as CD62P. Overall, our ex vivo production system was comparable to in vivo production system and produced platelet-like cells that were functionally superior to those produced in vitro. In future, the present ex vivo production system implementing xenogeneic bone marrow would offer a promising alternative for industrial-scale production of platelet-like cells.


Assuntos
Plaquetas/metabolismo , Células da Medula Óssea/citologia , Animais , Antígenos CD34/metabolismo , Plaquetas/citologia , Diferenciação Celular/efeitos dos fármacos , Humanos , Integrina beta3/metabolismo , Megacariócitos/citologia , Megacariócitos/metabolismo , Suínos , Trombina/farmacologia
10.
Medicine (Baltimore) ; 99(10): e19405, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32150090

RESUMO

Advanced gastric cancer has a poor prognosis because of advanced gastric cancer is prone to metastasis. It is urgent for us to find an indicator to predict the prognosis of gastric cancer in a timely fashion. Research has revealed that inflammation has an important role in predicting survival in some cancers. The purpose of this study was to evaluate the significance of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) on the prognosis of metastatic gastric cancer (GC).This was a retrospective review of 110 patients were at presentation diagnosed with stage IV metastatic GC and all patients received palliative chemotherapy between January 2012 and January 2016 at the Affiliated Hospital of Qingdao University. Pretreatment NLR and PLR, as well as clinicopathological characteristics were collected. Patients were divided into high and low groups according to the cutoff values for NLR and PLR. The Kaplan-Meier method was applied to estimate the overall survival (OS) and the Cox proportional hazards model to evaluate the related risk factors for OS. All tests were 2-tailed and a P < .05 was considered to indicate a statistically significant difference.One hundred ten patients were enrolled. Eighty-four patients were men, 24 patients were women, 61 patients were ≥65 years of age, and 49 patients were <65 years of age. The Eastern Cooperative Oncology Group (ECOG) score of most patients (n = 107) ranged from 0 to 1. Ten patients were human epidermal growth factor receptor 2 (HER2)-positive. Seventy-one patients presented with an elevated carcinoembryonic antigen (CEA) level and 49 patients had an elevated Carcinoembryonic 199 (CA-199) level. Fifty-two patients received first-line chemotherapy only. Nineteen patients received third-line or greater chemotherapy. One hundred patients chose dual drug chemotherapy. The median duration of follow-up was 11.6 months. Based on the receiver operating characteristic (ROC) curve, the optimal cut-off value for NLR and PLR was 2.48 and 143.39. Patients with high NLR and high PLR had poor overall survival compared with those who had low NLR and low PLR (P < .001 and P = .013, respectively). In univariate analysis, old age (P = .013), liver metastasis (P = .001), >1 metastatic sites (P = .028), higher NLR (P = .000), and higher PLR (P = .014) were identified as poor prognostic factors associated with OS. Our multivariate analysis had indicated that high NLR (hazard ratio [HR]: 1.617, 95% CI: 1.032-2.525, P = .036) and peritoneal metastasis (HR: 1.547, 95% CI:1.009-2.454, P = .045) was independent prognostic factors for overall survival; however, the PLR was not shown to be an independent prognostic factor.Our study suggested that the pretreatment NLR can be used as significant prognosis biomarker in metastatic gastric cancer patients receiving palliative chemotherapy.


Assuntos
Neoplasias Gástricas/mortalidade , Idoso , Biomarcadores Tumorais/sangue , Plaquetas/citologia , China , Feminino , Humanos , Linfócitos/citologia , Masculino , Metástase Neoplásica , Neutrófilos/citologia , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Análise de Sobrevida
11.
PLoS Comput Biol ; 16(3): e1007716, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32163405

RESUMO

The influence of red blood cell (RBC) deformability in whole blood on platelet margination is investigated using confocal microscopy measurements of flowing human blood and cell resolved blood flow simulations. Fluorescent platelet concentrations at the wall of a glass chamber are measured using confocal microscopy with flowing human blood containing varying healthy-to-stiff RBC fractions. A decrease is observed in the fluorescent platelet signal at the wall due to the increase of stiffened RBCs in flow, suggesting a decrease of platelet margination due to an increased fraction of stiffened RBCs present in the flow. In order to resolve the influence of stiffened RBCs on platelet concentration at the channel wall, cell-pair and bulk flow simulations are performed. For homogeneous collisions between RBC pairs, a decrease in final displacement after a collision with increasing membrane stiffness is observed. In heterogeneous collisions between healthy and stiff RBC pairs, it is found that the stiffened RBC is displaced most. The influence of RBC deformability on collisions between RBCs and platelets was found to be negligible due to their size and mass difference. For a straight vessel geometry with varying healthy-to-stiff RBC ratios, a decrease was observed in the red blood cell-free layer and platelet margination due to an increase in stiffened RBCs present in flow.


Assuntos
Plaquetas/citologia , Deformação Eritrocítica , Eritrócitos/citologia , Hematócrito , Modelos Biológicos , Técnicas Citológicas , Hemoglobinas/química , Humanos , Microscopia Confocal
12.
Korean J Radiol ; 21(4): 402-412, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32193888

RESUMO

OBJECTIVE: To evaluate the performance of predicting early recurrence using preoperative factors only in comparison with using both pre-/postoperative factors. MATERIALS AND METHODS: We retrospectively reviewed 549 patients who had undergone curative resection for single hepatcellular carcinoma (HCC) within Milan criteria. Multivariable analysis was performed to identify pre-/postoperative high-risk factors of early recurrence after hepatic resection for HCC. Two prediction models for early HCC recurrence determined by stepwise variable selection methods based on Akaike information criterion were built, either based on preoperative factors alone or both pre-/postoperative factors. Area under the curve (AUC) for each receiver operating characteristic curve of the two models was calculated, and the two curves were compared for non-inferiority testing. The predictive models of early HCC recurrence were internally validated by bootstrap resampling method. RESULTS: Multivariable analysis on preoperative factors alone identified aspartate aminotransferase/platelet ratio index (OR, 1.632; 95% CI, 1.056-2.522; p = 0.027), tumor size (OR, 1.025; 95% CI, 0.002-1.049; p = 0.031), arterial rim enhancement of the tumor (OR, 2.350; 95% CI, 1.297-4.260; p = 0.005), and presence of nonhypervascular hepatobiliary hypointense nodules (OR, 1.983; 95% CI, 1.049-3.750; p = 0.035) on gadoxetic acid-enhanced magnetic resonance imaging as significant factors. After adding postoperative histopathologic factors, presence of microvascular invasion (OR, 1.868; 95% CI, 1.155-3.022; p = 0.011) became an additional significant factor, while tumor size became insignificant (p = 0.119). Comparison of the AUCs of the two models showed that the prediction model built on preoperative factors alone was not inferior to that including both pre-/postoperative factors {AUC for preoperative factors only, 0.673 (95% confidence interval [CI], 0.623-0.723) vs. AUC after adding postoperative factors, 0.691 (95% CI, 0.639-0.744); p = 0.0013}. Bootstrap resampling method showed that both the models were valid. CONCLUSION: Risk stratification solely based on preoperative imaging and laboratory factors was not inferior to that based on postoperative histopathologic risk factors in predicting early recurrence after curative resection in within Milan criteria single HCC patients.


Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Aspartato Aminotransferases/sangue , Plaquetas/citologia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Razão de Chances , Período Pré-Operatório , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco
13.
Transfusion ; 60(4): 806-814, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32159862

RESUMO

BACKGROUND: During platelet storage, there are extensive changes in cytoskeleton and phosphatidylserine exposure. The intrinsic mitochondrial pathway of apoptosis, activated in stored platelets, is a major mediator these changes. Cofilin-1 is an effector of actin reorganization. We examined the effect of cofilin-1 deficiency on cytoskeleton and phosphatidylserine exposure during storage and following activation of apoptosis. METHODS AND RESULTS: We assessed actin filaments by Alexa-647-phalloidin and phosphatidylserine exposure by fluorescein isothiocyanate-lactadherin by fluorescence microscopy. In fresh platelets, actin filaments are distributed in the subcortical region, and they do not express phosphatidylserine in the outer surface. In stored platelets, there is retraction of actin filaments from the subcortical region with increased phosphatidylserine expression. These changes are seen in 20% of platelets of 6 days old and increases further with storage. Treatment with ABT-737, which activates the mitochondrial apoptosis, induces similar cytoskeletal changes in actin filaments with increased phosphatidylserine. Cofilin-1 is activated in stored platelets as well as in ABT-737 treated platelets by dephosphorylation. In cofilin-1 deficient murine platelets actin filaments are abnormal and ABT-737 induces less phosphatidylserine. Despite these changes in vitro, platelet survival of cofilin-1 deficient platelets in mice was not significantly different from their wild-type controls. CONCLUSION: These results show that cofilin-1 plays a role in apoptosis-induced actin rearrangement and phosphatidylserine exposure during storage. Despite the defects in platelet cytoskeleton and phosphatidylserine exposure in cofilin-1-deficient platelets, the in vivo life span of platelets is similar to littermate controls, indicating multiple redundant pathways for the clearance of platelets in vivo.


Assuntos
Actinas/metabolismo , Plaquetas/citologia , Cofilina 1/fisiologia , Actinas/efeitos dos fármacos , Animais , Apoptose , Compostos de Bifenilo/farmacologia , Preservação de Sangue , Cofilina 1/deficiência , Citoesqueleto/metabolismo , Humanos , Camundongos , Nitrofenóis/farmacologia , Fosfatidilserinas/metabolismo , Piperazinas/farmacologia , Sulfonamidas/farmacologia
14.
Transfusion ; 60(5): 986-996, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32181889

RESUMO

BACKGROUND: Platelets have the highest bacterial contamination risk of all blood components, and septic transfusion reactions remain a problem. A good estimate of contamination rates could provide information about residual risk and inform optimal testing strategies. We performed a systematic review and meta-analysis of platelet contamination rates by primary culture. STUDY DESIGN AND METHODS: A literature search in December 2019 identified articles on platelet contamination rates using primary culture. We used meta-analysis to estimate the overall rate of contamination and meta-regression to identify heterogeneity. We studied the following sources of heterogeneity: collection method, sample volume, positivity criteria, and study date. Contamination rate estimates were obtained for apheresis (AP), platelet rich plasma (PRP), and buffy coat (BC) collection methods. RESULTS: The search identified 6102 studies, and 22 were included for meta-analysis. Among these 22 studies, there were 21 AP cohorts (4,072,022 components), 4 PRP cohorts (138,869 components), and 15 BC cohorts (1,474,679 components). The overall mean contamination rate per 1000 components was 0.51 (95% CI: 0.38-0.67) including AP (0.23, 95% CI: 0.18-0.28), PRP, (0.38, 95% CI: 0.15-0.70), and BC (1.12, 95% CI: 0.51-1.96). There was considerable variability within each collection method. Sample volume, positivity criteria, and publication year were significant sources of heterogeneity. CONCLUSION: The bacterial contamination rate of platelets by primary culture is 1 in 1961. AP and PRP components showed a lower contamination rate than BC components. There is clinically significant between-study variability for each method. Larger sample volumes increased sensitivity, and bacterial contamination rates have decreased over time.


Assuntos
Infecções Bacterianas/sangue , Remoção de Componentes Sanguíneos/estatística & dados numéricos , Plaquetas/microbiologia , Contaminação de Medicamentos/estatística & dados numéricos , Transfusão de Plaquetas/estatística & dados numéricos , Cultura Primária de Células/estatística & dados numéricos , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/transmissão , Técnicas Bacteriológicas , Remoção de Componentes Sanguíneos/efeitos adversos , Transfusão de Componentes Sanguíneos/efeitos adversos , Transfusão de Componentes Sanguíneos/estatística & dados numéricos , Plaquetas/citologia , Células Cultivadas , Humanos , Transfusão de Plaquetas/efeitos adversos , Plasma Rico em Plaquetas/microbiologia , Cultura Primária de Células/métodos , Cultura Primária de Células/normas , Reação Transfusional/epidemiologia , Reação Transfusional/microbiologia
15.
Transfusion ; 60(4): 769-778, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32187691

RESUMO

BACKGROUND: Platelet engraftment following cord blood (CB) transplantation remains a significant hurdle to this day. The uncontrolled growth of ice, a process referred to as ice recrystallization, is one of several mechanisms that lead to cell loss and decreased potency during freezing and thawing. We hypothesized that reducing cell damage induced by ice recrystallization in CB units (CBUs) would reduce losses of stem and progenitor cells and therefore improve engraftment. We previously demonstrated that the ice recrystallization inhibitor (IRI) N-(2-fluorophenyl)-D-gluconamide (IRI 2) increases the postthaw recovery of CB progenitors. Herein, we set out to ascertain whether IRI 2 can enhance platelet and bone marrow engraftment activity of hematopoietic stem cells (HSCs) in cryopreserved CBUs using a serial transplantation model. STUDY DESIGN AND METHODS: CBUs were processed following standard volume/red blood cell reduction procedure and portions frozen with dimethyl sulfoxide (DMSO) supplemented or not with IRI 2. Thawed CB samples were serially transplanted into immunodeficient mice. RESULTS: Our results show that supplementation of DMSO with IRI 2 had several beneficial effects. Specifically, higher levels of human platelets were observed in the peripheral blood (p < 0.05; n = 4) upon transplant of CBUs preserved with the IRIs. In addition, human BM chimerism and the number of human CFU progenitors in the bone marrow were superior in IRI 2 recipients compared to DMSO recipients. Moreover, IRI 2 had no negative impact on the multilineage differentiation and self-renewal activities of HSCs. DISCUSSION: Taken together, these results demonstrate that supplementation of a hematopoietic graft with IRI can improve the postthaw engraftment activities of HSCs.


Assuntos
Plaquetas/citologia , Criopreservação/métodos , Sangue Fetal/transplante , Sobrevivência de Enxerto , Gelo/efeitos adversos , Animais , Crioprotetores/farmacologia , Cristalização , Dimetil Sulfóxido/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Camundongos
16.
Transfusion ; 60(5): 1050-1059, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32187695

RESUMO

BACKGROUND: Our previous study showed that ultraviolet C (UVC) from xenon (Xe) flash without any photoreactive compounds inactivated bacteria in platelet concentrates (PCs) with less damage to platelets (PLTs) as compared with Xe flash containing ultraviolet A, ultraviolet B, and visible light. Here, we report a UVC irradiation system for PCs under flow conditions consisting of a flow path-irradiation sheet, a peristaltic pump, and a collection bag. STUDY DESIGN AND METHODS: Platelet concentrates containing Ringer's solution (R-PCs) inoculated with bacteria were injected into a flow path sheet using a peristaltic pump, being irradiated with UVC from Xe flash. The quality of the irradiated PCs containing platelet additive solution (PAS-PCs) was assessed based on PC variables, PLT surface markers, and aggregation ability. RESULTS: Streptococcus dysgalactiae (12 tests) and Escherichia coli (11) were all negative on bacterial culture, while Staphylococcus aureus (12) and Klebsiella pneumoniae (14) grew in one and two R-PCs, respectively. Bacillus cereus spores were inactivated in 7 of 12 R-PCs. PC variables became significantly different between irradiated and nonirradiated PAS-PCs. P-selectin, first procaspase-activating compound (PAC-1) binding, and phosphatidylserine increased by irradiation. Aggregability stimulated by adenosine diphosphate, collagen, or thromboxane A2 increased in the irradiated PAS-PCs, while that by thrombin became smaller compared with nonirradiated controls. CONCLUSION: This newly developed system inactivated bacteria including spores in R-PCs. PAS-PCs irradiated by this system retained acceptable in vitro quality and aggregability. Usage of a peristaltic pump instead of agitator during irradiation may enable this system to be directly combined with an apheresis blood cell separator.


Assuntos
Plaquetas/citologia , Preservação de Sangue , Desinfecção/instrumentação , Viabilidade Microbiana , Raios Ultravioleta , Xenônio/farmacologia , Bacillus cereus/efeitos dos fármacos , Bacillus cereus/fisiologia , Bacillus cereus/efeitos da radiação , Bactérias/efeitos dos fármacos , Bactérias/efeitos da radiação , Remoção de Componentes Sanguíneos , Plaquetas/efeitos dos fármacos , Plaquetas/efeitos da radiação , Preservação de Sangue/instrumentação , Preservação de Sangue/métodos , Segurança do Sangue/instrumentação , Segurança do Sangue/métodos , Desinfecção/métodos , Contaminação de Medicamentos/prevenção & controle , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Escherichia coli/efeitos da radiação , Humanos , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/fisiologia , Klebsiella pneumoniae/efeitos da radiação , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Viabilidade Microbiana/efeitos da radiação , Soluções para Preservação de Órgãos/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Agregação Plaquetária/fisiologia , Agregação Plaquetária/efeitos da radiação , Controle de Qualidade , Solução de Ringer/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Staphylococcus aureus/efeitos da radiação , Streptococcus/efeitos dos fármacos , Streptococcus/fisiologia , Streptococcus/efeitos da radiação
17.
Transfusion ; 60(5): 1042-1049, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32187700

RESUMO

BACKGROUND: Some jurisdictions require leukoreduction of cellular blood components. The only whole blood collection set with a platelet-saving filter uses citrate-phosphate-dextrose (CPD) as storage solution. Substituting CPD with citrate-phosphate-dextrose-adenine (CPDA-1) increases shelf life from 21 to 35 days. This would simplify prehospital and rural resupply and reduce wastage. We investigated in vitro quality and hemostatic properties of CPDA-1 whole blood leukoreduced with a platelet-saving filter. STUDY DESIGN AND METHODS: CPDA-1 whole blood was leukoreduced using a platelet-saving filter and stored 35 days. EDQM requirements, hematology, metabolic parameters, thromboelastography, light transmission aggregometry, fibrinogen, factor VIII, and interleukin-6 were measured on Days 0, 1, 14, 21, and 35 and compared to non-leukoreduced blood. RESULTS: All units met EDQM requirements. Leukoreduction yielded residual white blood cell count <1 × 106 and 87% platelet recovery on Day 1. It caused reduction in thromboelastography parameters, but not aggregometry response. No hemolysis >0.8% was observed. Factor VIII was higher on Day 35 in the leukoreduced group, 37.9 (95% CI: 26.0, 49.8) versus 13.8 (9.4, 18.2) IU/dL. In both groups, aggregation was significantly reduced by Day 14. Thromboelastography showed remaining platelet activity on Day 35, MA 46.9 (42.1, 51.7) in the leukoreduced and 44.3 (39.6, 49.0) mm in the non-leukoreduced group. Fibrinogen was within reference ranges at Day 35 (>2 g/dL). Interleukin-6 was not detectable. CONCLUSION: Leukoreducing CPDA-1 whole blood with a platelet-saving filter did not compromise hemostatic properties. We encourage development of a single bag CPDA-1 whole blood collection set with in-line platelet-saving filter.


Assuntos
Adenina/química , Preservação de Sangue/métodos , Coleta de Amostras Sanguíneas/métodos , Citratos/química , Temperatura Baixa , Glucose/química , Procedimentos de Redução de Leucócitos/métodos , Fosfatos/química , Adenina/farmacologia , Sangue/efeitos dos fármacos , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Preservação de Sangue/normas , Coleta de Amostras Sanguíneas/normas , Citratos/farmacologia , Filtração/métodos , Glucose/farmacologia , Hemólise/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Humanos , Técnicas In Vitro , Procedimentos de Redução de Leucócitos/normas , Fosfatos/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Contagem de Plaquetas , Controle de Qualidade , Refrigeração/métodos
18.
J Photochem Photobiol B ; 204: 111782, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32062389

RESUMO

BACKGROUND: Ultraviolet (UV) fluorescent lamp (FL) was applied in mainstream riboflavin photochemical method (RPM) to inactivate pathogens in blood components. Low UV irradiance emitted by UV-FL resulted in more time to achieve effective inactivation. MATERIALS AND METHODS: A novel light emitting diode (LED) UV illumination with adjustable irradiance was developed by us. Two strains of drug-resistant bacteria (DRB), pan-drug resistant Acinetobacter baumannii (PDRAB) and methicillin-resistant Staphylococcus aureus (MRSA) were cultured and used for evaluating the inactivation effectiveness of RPM using UV-LED or UV-FL against DRB in plasma or platelets. Three plasma factors and four platelet parameters were measured after treatments. RESULTS: There was a linear relationship between UV-LED irradiance and electric current, the minimum UV irradiance was 24 mW/cm2, and the maximum was 258 mW/cm2. At the same UV dose of 15 J/cm2, inactivation effectiveness of UV-LED with 258 mW/cm2 against PDRAB in plasma or platelets were comparable to that of UV-FL with 16 mW/cm2, both above 98%. UV-FL treatment required 10-15 min, but UV-LED only required 1-2 min. However, MRSA showed a resistance to UV-LED (inactivation effectiveness was around 40%) compared with UV-FL (inactivation effectiveness was above 98%). The retention of fibrinogen, factor V, factor VII in plasma and platelet counts in platelets with UV-LED treatment were significantly higher than UV-FL at the same UV dose. CONCLUSION: The treatment of RPM using UV-LED with high UV irradiance was able to dramatically shorten inactivation time against PDRAB in plasma or platelets and improve retention of blood components compared with UV-FL.


Assuntos
Proteínas Sanguíneas/metabolismo , Riboflavina/química , Raios Ultravioleta , Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/efeitos da radiação , Plaquetas/citologia , Plaquetas/efeitos dos fármacos , Plaquetas/efeitos da radiação , Farmacorresistência Bacteriana/efeitos dos fármacos , Fator V/metabolismo , Fibrinogênio/metabolismo , Humanos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos da radiação , Contagem de Plaquetas , Riboflavina/farmacologia
19.
Int J Nanomedicine ; 15: 901-912, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32103945

RESUMO

Background: Aortic valve disease is the most common valvular heart disease leading to valve replacement. The efficacy of pharmacological therapy for aortic valve disease is limited by the high mechanical stress at the aortic valves impairing the binding rate. We aimed to identify nanoparticle coating with entire platelet membranes to fully mimic their inherent multiple adhesive mechanisms and target the sclerotic aortic valve of apolipoprotein E-deficient (ApoE-/-) mice based on their multiple sites binding capacity under high shear stress. Methods: Considering the potent interaction of platelet membrane glycoproteins with components present in sclerotic aortic valves, platelet membrane-coated nanoparticles (PNPs) were synthetized and the binding capacity under high shear stress was evaluated in vitro and in vivo. Results: PNPs demonstrated effectively adhering to von Willebrand factor, collagen and fibrin under shear stresses in vitro. In an aortic valve disease model established in ApoE-/- mice, PNPs exhibited good targeting to sclerotic aortic valves by mimicking platelet multiple adhesive mechanisms. Conclusion: PNPs could provide a promising platform for the molecular diagnosis and targeting treatment of aortic valve disease.


Assuntos
Plaquetas/citologia , Doenças das Valvas Cardíacas/tratamento farmacológico , Nanopartículas/química , Nanopartículas/metabolismo , Animais , Valva Aórtica/efeitos dos fármacos , Valva Aórtica/patologia , Apolipoproteínas E/genética , Plaquetas/química , Membrana Celular/química , Colágeno/metabolismo , Modelos Animais de Doenças , Fibrina/metabolismo , Cardiopatias Congênitas , Doenças das Valvas Cardíacas/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Nanopartículas/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Esclerose , Estresse Mecânico , Fator de von Willebrand/metabolismo
20.
Soft Matter ; 16(8): 2141-2148, 2020 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-32016231

RESUMO

Poly(l-lactic acid) (PLLA) scaffolds have been used in regenerative medicine, however, they commonly suffer from low flexibility, restricting their application in the repair and reconstruction of soft tissues. In this study, poly(l-lactide-co-ε-caprolactone) (PLCL) copolymers were examined to modulate the elasticity of PLLA with the random presence of CL units in PLLA. Thermodynamic analysis revealed that the introduction of PCL could significantly decrease the melting point and glass transition temperature of PLLA, benefiting the extrusion and printing of PLCL. Diverse scaffolds with designed architectures including porous cubes with or without large holes, cambered plates with holes and round tubes could be easily constructed by 3D printing. In the process of elastic deformation, the maximum elastic stress of the copolymer scaffold was obviously increased from 19.6 to 31.5 MPa when the relative content of PCL was increased to 70%, while the elongation at break was evidently increased from 388% to about 1974%. The Young's modulus of PLCL was also significantly decreased (P < 0.05) in comparison with that of PLLA. PLCL scaffolds have good platelet and endotheliocyte adhesion ability and no obvious hemolysis was observed. In vivo subcutaneous implantation of PLCL scaffolds demonstrated superior biocompatibility. Collectively, this work highlights that copolymerization of PCL segments into PLLA is an effective approach to tune the 3D printability and the stiffness and elasticity of PLLA scaffolds. PLCL scaffolds hold great promise for the regeneration of soft tissues including but not limited to cartilage, myocardium, muscle, tendon and nervous tissues.


Assuntos
Poliésteres/química , Tecidos Suporte/química , Animais , Materiais Biocompatíveis/química , Fenômenos Biomecânicos , Plaquetas/citologia , Adesão Celular , Proliferação de Células , Elasticidade , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Impressão Tridimensional , Coelhos , Engenharia Tecidual/instrumentação
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